The Histomorphologic Spectrum of Primary Cutaneous Diffuse Large B-Cell Lymphoma: A Study of 79 Cases

Abstract

Primary cutaneous large B-cell lymphomas (PCLBCL) have historically been a matter of debate in the literature. The 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification scheme segregated cutaneous B-cell lymphomas into 3 groups: primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center cell lymphoma, and primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), "leg type" (PCDLBCL-LT). Additionally, the WHO-EORTC classification scheme utilized the term PCLBCL "other" not otherwise specified (NOS) type for rare cases of PCLBCL not belonging to either the "leg type" or the primary cutaneous follicle center cell lymphoma group. In this study, we retrospectively assessed the histomorphologic features of 79 cases of PCDLBCLs, including those of "leg type" and "other" NOS type, to further categorize the histologic spectrum of these unusual cutaneous neoplasms. The histologic diagnosis of PCLBCL usually poses little diagnostic difficulty; however, some cases may adopt unusual or unfamiliar appearances mimicking other lymphoproliferative disorders or other malignant neoplasms. Seventy-nine cases, occurring in 37 men and 42 women, aged 34-94 years, were analyzed. Fifty-three cases were classified as "leg type" and 26 cases were classified as "other" NOS type using the WHO-EORTC classification. Of the 53 cases classified as "leg type," 33 were women and 20 were men; of the 26 cases of "other" NOS type, 9 were women and 17 were men. In the "leg type" category, 31 cases were located on the lower extremities, 5 cases on the face, 5 cases on the arm, 3 cases on the chest, 2 cases on the shoulder, 2 cases on the back, 1 case on the trunk, 1 case on the buttock, 1 case on the supraclavicular area, 1 case on the head, and 1 case on the flank. Of the "other" NOS type category, 8 cases were located on the face, 5 cases on the shoulder, 3 cases on the head, 2 cases on the abdomen, 2 cases on the chest, 1 case on the trunk, 1 on the vulva, 1 on the axilla, 1 on the back, 1 on the neck, and 1 on the hip. Most cases assessed showed the classic morphologic appearance of PCDLBCL, but cases mimicking Burkitt lymphoma (starry-sky pattern), natural killer-cell (NK) lymphoma, mycosis fungoides (epidermotropism), low-grade B-cell lymphomas, epithelial malignancies, and Merkel cell carcinoma were encountered in this series. The high frequency of these rare histologic patterns can be explained by a bias associated with consultation practice. Careful histologic examination and immunohistochemical stains were used to establish the correct diagnosis. The differential diagnosis of PCDLBCL is broad and difficult to define histologically. Knowledge of these rare histologic variants is necessary to avoid misinterpretation of these cases as nonlymphoid malignancies.

Pitfalls in the Diagnosis of Cutaneous Lymphoma

“…Furthermore, skin involvement may precede the diagnostic pulmonary involvement in 16% of cases, and cutaneous involvement may be the primary manifestation of the disease in up to one third of the patients. 51 Rarely, the angiocentric/angioinvasive pattern has been documented in other cutaneous B-cell lymphomas such as diffuse large B-cell lymphoma, leg type (DLBCLleg type), diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), 41 methotrexate-induced cutaneous DLBCL, 52 primary cutaneous T-cell-rich B-cell lymphoma (TCRBCL). 53…”

“…3,44,45 Regardless of the lineage of intraepidermal lymphocytes, some of these B-cell lymphomas histologically and clinically mimic MF in the form of a pruritic rash as the primary clinical presentation. 3,36,37,45 Amongst the 8 cases, where true B-cell epidermotropism was seen, 4 had systemic involvement and 4 of the 8 were marginal zone lymphomas (MZLs) 3,[36][37][38][39][40][41] (Table 3). Involvement of pilosebaceous unit epithelium and/or epidermis was seen in 4 cases in a series of 15 cases of cutaneous B-cell MZL.…”

“…35 Isolated reports of B-cell lymphomas exhibiting epidermotropism and mimicking MF have been cited in literature. 3,[36][37][38][39][40][41][42][43][44][45] In 8 of these epidermotropic B-cell lymphomas, the neoplastic B cells involved the epidermis as demonstrated by IHC (Table 3), 3,[36][37][38][39][40][41] whereas in 2 of them, the type of epidermotropic cells was not specified. 42,43 In 5 cases, the intraepidermal cells were reactive T cells in an otherwise B-cell lymphoma, giving the false impression of T-cell morphology.…”

Pathologic Diagnosis of Cutaneous Lymphomas

“…An uncommon histologic presentation includes a spindle cell and an anaplastic variant. 107 Moreover, an angiocentric infiltrate 108 and expression of CD30 have been described. 109,110 Immunophenotype and clonality The tumor cells are positive for CD20, CD79a, and PAX-5 and show a strong expression for bcl-2 and multiple myeloma oncogene-1 (MUM-1).…”

Cutaneous B-Cell Lymphoproliferative Disorders

“…Some may have spindle cell features (although many of these cases are now thought to represent PCFCL). 63 Clinical data are required because it is unclear that DLBCL, leg type, has any easily documented unique features. Other considerations include other specific types of large B-cell lymphomas, a subject much too large to review here.…”